Background/Purpose: Hydrocodone, codeine, oxycodone, and tramadol are frequently prescribed for moderate pain in adolescents. However, pharmacokinetic and pharmacodynamic differences between these short-acting opioids could affect their relative safety. Although tramadol, which is both a serotonin/norepinephrine reuptake inhibitor and a μ-opioid agonist, has been considered a safer opioid, limited data support this perception. We aimed to compare the occurrence of opioid-related adverse events for adolescents without cancer or other severe conditions taking commonly prescribed short-acting opioids.

Methods: Retrospective cohort study in Tennessee Medicaid, 1999-2011. We studied Medicaid enrollees 12 to 17 years of age without cancer, other severe conditions or evidence of substance abuse with filled prescriptions for study opioids. Exposure was defined as current or recent use of hydrocodone, codeine, oxycodone, and tramadol. The primary outcome was an emergency department visit, hospital admission, or death adjudicated after review of medical records as plausibly related to opioid use, classified as serious if there was hospitalization or opioid-related escalation of care. Propensity-score adjusted hazard ratios (HRs) were calculated with hydrocodone as the reference category.

Results: The incidence of opioid-related adverse events per 10,000 person-years of opioid exposure was 317.0 for tramadol (47/1,483 person-years), 229.7 for oxycodone (43/1,872), 91.2 for codeine (58/6,359), and 97.5 for hydrocodone (127 events/13,026). The adjusted HR for tramadol was 2.72 (1.84-4.03), with a comparable increase for serious events (HR = 2.92 [1.45-5.88]). Risk for codeine was not significantly increased (HR = 1.35 [0.95-1.90]). The risk for all events was increased for oxycodone (HR = 1.77 [1.17-2.68]), but that for serious events was not (HR = 0.94 [0.32-2.73]). The increased risk for tramadol was consistently present in multiple sensitivity analyses to reduce residual confounding or misclassification and in an analysis with codeine as the reference category (all events: HR = 1.86 [1.16-2.98]; serious events: HR = 2.74 [1.33-5.64]).

Conclusion: In this cohort of adolescents without cancer or other severe conditions prescribed short-acting opioids, the incidence of opioid-related adverse events for tramadol was consistently greater than that for either hydrocodone or codeine, including for the more serious events leading to hospitalization or escalation of care.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/individual-short-acting-opioids-and-the-risk-of-opioid-related-adverse-events-in-adolescents/